Blood samples are one of medicine’s most powerful diagnostic tools, but taking and storing liquid blood samples is expensive and time consuming. To bring down costs and broaden the use of samples, researchers at Uppsala University are studying the potential for using millimeter-wide drops of dried blood on filter paper as an alternative means of collecting and storing samples.
Go in for a medical exam and odds are that the doctor will at some point order a blood draw because the bloodstream is a treasure trove of medical data. By looking at various protein or RNA biomarkers, for example, physicians can find early signs of illnesses that can be treated before they even produce symptoms. Ideally, if enough samples can be taken at frequent intervals, doctors would have a baseline of a patient’s normal state of health, a record of the progression of a disease, and a better understanding of how to treat it.
The problem is taking and storing blood samples is expensive, time consuming, and requires skilled technicians. Collecting a blood sample involves going to an office or clinic where it will be taken by a trained nurse. The venous blood must then be sent to a lab for centrifuging and analysis or stored in a special freezer at a temperature of -80° C (-112° F).
Because of all this, institutions like the Uppsala University Hospital often save only about one percent of blood samples taken in its biobank after analysis, and sampling isn’t nearly as frequent as diagnosticians and researchers would like.
The Uppsala scientists are looking at dried blood spots (DBS) as an alternative. To do this, they looked at blood spots that were collected from newborn babies in routine screening for congenital metabolic disorders. These samples were preserved for up to 30 years in biobanks in Sweden and Denmark at temperatures from -24° C (-11° F) to 4° C (39° F) and were compared against wet plasma samples stored at -70° C (-94° F) for about the same period of time.
The researchers looked at levels of 92 proteins that are relevant in cancer diagnosis by means of proximity extension assay, which uses matched pairs of antibodies linked to unique oligonucleotides that bond to specific proteins. In addition, they measured the effects of long-term storage and the effect of drying on protein detection.
What they found was that, even after being dried for decades, most samples remained almost completely unaltered. However, some proteins showed signs of losing up to half their quantity after 10 to 50 years. They also discovered that in comparison to wet blood plasma that needs to be stored at temperatures of -70° C (-94° F), dried samples do well at -24° C (-11° F).
“Our conclusion is that we can measure levels of 92 proteins with very high precision and sensitivity using [proximity extension assay] technology in the tiny, punched-out discs from a dried blood spot,” says Johan Björkesten, a doctoral student at Uppsala University. “The actual drying process has a negligible effect on the various proteins and the effect is reproducible, which means that it can be included in the calculation.”
According to the team, the use of dried samples would allow blood samples to be used more often for routine health checks. Because there’s no need for taking venous blood to get a few drops, patients can take their own samples by pricking their fingers, and instead of visiting a clinic they can post the papers to their healthcare provider.
In addition, because the large, expensive medical freezers aren’t needed, and more dried samples can be kept for longer periods of time, which would provide doctors and researchers with much larger bio-databases.
“This has several implications,” says Ulf Landegren, Professor of Molecular Medicine and head of the Molecular Tools research group. “First, you can prick your own finger and send in a dried blood spot by post. Second, at a minimal cost, it will be possible to build gigantic biobanks of samples obtained on a routine clinical basis. This means that samples can be taken before the clinical debut of a disease, to identify markers of value for early diagnosis, improving the scope for curative treatment.”